chr1-24182584-T-A

Position:

• chr1-24182584-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_170743.4(IFNLR1):​c.59-1730A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 152,092 control chromosomes in the GnomAD database, including 8,601 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.31 (8601 hom., cov: 33)
• Consequence: IFNLR1 NM_170743.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.286

Genes affected

IFNLR1 (HGNC:18584): (interferon lambda receptor 1) The protein encoded by this gene belongs to the class II cytokine receptor family. This protein forms a receptor complex with interleukine 10 receptor, beta (IL10RB). The receptor complex has been shown to interact with three closely related cytokines, including interleukin 28A (IL28A), interleukin 28B (IL28B), and interleukin 29 (IL29). The expression of all three cytokines can be induced by viral infection. The cells overexpressing this protein have been found to have enhanced responses to IL28A and IL29, but decreased response to IL28B. Three alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IFNLR1	NM_170743.4	c.59-1730A>T		intron_variant		ENST00000327535.6
IFNLR1	NM_173064.3	c.59-1730A>T		intron_variant
IFNLR1	NM_173065.3	c.59-1730A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFNLR1	ENST00000327535.6	c.59-1730A>T		intron_variant		1	NM_170743.4	P1

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47491 AN: 151974 Hom.: 8591 Cov.: 33

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.320

Gnomad AMR AF: 0.516

Gnomad ASJ AF: 0.325

Gnomad EAS AF: 0.493

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.350

Gnomad MID AF: 0.229

Gnomad NFE AF: 0.355

Gnomad OTH AF: 0.330

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.312 AC: 47506 AN: 152092 Hom.: 8601 Cov.: 33 AF XY: 0.316 AC XY: 23456 AN XY: 74322

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.517

Gnomad4 ASJ AF: 0.325

Gnomad4 EAS AF: 0.492

Gnomad4 SAS AF: 0.260

Gnomad4 FIN AF: 0.350

Gnomad4 NFE AF: 0.355

Gnomad4 OTH AF: 0.326

Alfa AF: 0.329 Hom.: 1272

Bravo AF: 0.323

Asia WGS AF: 0.360 AC: 1251 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.7
DANN	Benign	0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10903047; hg19: chr1-24509074; COSMIC: COSV59525721;